Due to change in the national policy of medications

Preclinical studies showed that metronomic chemotherapy can induce tumor regression secondary to apoptosis of the tumor blood vessels. This effect was increased by combining metronomic chemotherapy with anti-angiogenic drugs. Metronomic chemotherapy has already proved clinical effects too, especially on patients with breast or prostate carcinoma. This study is aimed to test the efficacy of an experimental metronomic chemotherapy regimen in a cohort of patients with ovarian cancer. Patients will receive the proposed regimen as maintenance treatment following response induction by the conventional maximal tolerated dose (MTD) regimen of Carboplatin and Paclitaxel. Our regimen will include Cytophosphan combined with two agents which are expected to act as indirect angiogenic inhibitors: (a) celecoxib, as a selective COX-2 inhibitor and (b) low-dose Methotrexate, as successfully practiced for suppressing the inflammatory manifestations of rheumatoid arthritis. All components of our regimen will be administered orally and continuously for one year based on the hypothesis that its anti-angiogenic properties will be able to suppress the recovery of residual disease, thus extending the time to progression (TTP), and possibly the overall survival as well.

Inclusion Criteria:

1. Histologic proof of papillary-serous ovarian cancer or 1ary peritoneal carcinomatosis.
2. Histological grade III.
3. Original disease in stage III.
4. ECOG performance status: 0-2.
5. Age: 20-80 years.
6. Previous chemotherapy with paclitaxel and carboplatin (only).
7. Previous cyto-reductive surgery.
8. Clinical Complete Response (both physically and by imaging).
9. CA 125 should be either normalized (in at least 50 patients) or while still in decreasing values at monthly measurements.
10. CBC at normal values or with any toxicity at a grade limited to I by NCIC-CTC.
11. Liver and renal functions < 1.5 upper normal limits (UNL) by SMA.
12. The patient's signature on the informed consent.

Exclusion Criteria:

1. Mucinous type ovarian carcinoma.
2. Histological Grade I-II.
3. Current continuous treatment by steroids or by NSAIDs, or by anti-coagulants for "non protocol" reasons.
4. Previous history of active peptic ulcer.
5. Current participation in any other treatment study.